CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent
Abstract A series of 5-(substituted benzylidene) thiazolidine-2,4-dione and coumarin hybrids (I-1 to I-16) were designed and synthesized to explore key structural requirements for effective α-glucosidase inhibitors. Molecular docking studies were conducted to investigate their interactions with vari...
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Nature Portfolio
2025-02-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88944-y |
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| author | Anchal Sharma Anmol Narang Nitish Kumar Rupali Rana Megha Pooja Muskan Dhir Harmandeep Kaur Gulati Jyoti Aanchal Khanna Jatinder Vir Singh Sukhraj Kaur Preet Mohinder Singh Bedi |
| author_facet | Anchal Sharma Anmol Narang Nitish Kumar Rupali Rana Megha Pooja Muskan Dhir Harmandeep Kaur Gulati Jyoti Aanchal Khanna Jatinder Vir Singh Sukhraj Kaur Preet Mohinder Singh Bedi |
| author_sort | Anchal Sharma |
| collection | DOAJ |
| description | Abstract A series of 5-(substituted benzylidene) thiazolidine-2,4-dione and coumarin hybrids (I-1 to I-16) were designed and synthesized to explore key structural requirements for effective α-glucosidase inhibitors. Molecular docking studies were conducted to investigate their interactions with various targets, including DPP-4, α-glucosidase, α-amylase, and PPAR-γ. The docking scores and binding energies indicated that Compound I-1 emerged as the optimal scaffold for drug design, excluding α-amylase. Compound I-1 was synthesized based on the insights gained from molecular docking and simulations, which helped predict interactions and identify critical structural features. Pharmacokinetic properties were evaluated through drug-likeness and ADMET studies. Additionally, density functional theory (DFT) analyses were performed to assess the stability and reactivity of potential diabetes mellitus drug candidates. Dynamic simulation studies further elucidated the stability and interaction dynamics of the top-ranked compound I-1. In vitro evaluation against the α-glucosidase enzyme yielded an IC 50 value of 1.49 µg/ml. In vivo studies demonstrated that Compound I-1 significantly reduced blood glucose levels, with values of 94.15 mg/dL and 74.60 mg/dL at doses of 10 mg/kg and 20 mg/kg, respectively. Furthermore, Compound I-1, like Acarbose, resulted in significant reductions in ALT, AST, ALP, urea, LDH, and creatinine levels, suggesting improved liver and kidney function. |
| format | Article |
| id | doaj-art-8dc43daf49694c2cb87de57f6fcc7e31 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-8dc43daf49694c2cb87de57f6fcc7e312025-02-09T12:32:49ZengNature PortfolioScientific Reports2045-23222025-02-0115112210.1038/s41598-025-88944-yCADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agentAnchal Sharma0Anmol Narang1Nitish Kumar2Rupali Rana3Megha4Pooja5Muskan Dhir6Harmandeep Kaur Gulati7Jyoti8Aanchal Khanna9Jatinder Vir Singh10Sukhraj Kaur11Preet Mohinder Singh Bedi12Department of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Microbiology, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Chemistry, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityDepartment of Microbiology, Guru Nanak Dev UniversityDepartment of Pharmaceutical Sciences, Guru Nanak Dev UniversityAbstract A series of 5-(substituted benzylidene) thiazolidine-2,4-dione and coumarin hybrids (I-1 to I-16) were designed and synthesized to explore key structural requirements for effective α-glucosidase inhibitors. Molecular docking studies were conducted to investigate their interactions with various targets, including DPP-4, α-glucosidase, α-amylase, and PPAR-γ. The docking scores and binding energies indicated that Compound I-1 emerged as the optimal scaffold for drug design, excluding α-amylase. Compound I-1 was synthesized based on the insights gained from molecular docking and simulations, which helped predict interactions and identify critical structural features. Pharmacokinetic properties were evaluated through drug-likeness and ADMET studies. Additionally, density functional theory (DFT) analyses were performed to assess the stability and reactivity of potential diabetes mellitus drug candidates. Dynamic simulation studies further elucidated the stability and interaction dynamics of the top-ranked compound I-1. In vitro evaluation against the α-glucosidase enzyme yielded an IC 50 value of 1.49 µg/ml. In vivo studies demonstrated that Compound I-1 significantly reduced blood glucose levels, with values of 94.15 mg/dL and 74.60 mg/dL at doses of 10 mg/kg and 20 mg/kg, respectively. Furthermore, Compound I-1, like Acarbose, resulted in significant reductions in ALT, AST, ALP, urea, LDH, and creatinine levels, suggesting improved liver and kidney function.https://doi.org/10.1038/s41598-025-88944-yMolecular dockingMolecular dynamics simulationDFT investigationα-glucosidaseα-amylaseDPP-4 |
| spellingShingle | Anchal Sharma Anmol Narang Nitish Kumar Rupali Rana Megha Pooja Muskan Dhir Harmandeep Kaur Gulati Jyoti Aanchal Khanna Jatinder Vir Singh Sukhraj Kaur Preet Mohinder Singh Bedi CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent Scientific Reports Molecular docking Molecular dynamics simulation DFT investigation α-glucosidase α-amylase DPP-4 |
| title | CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| title_full | CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| title_fullStr | CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| title_full_unstemmed | CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| title_short | CADD based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| title_sort | cadd based designing and biological evaluation of novel triazole based thiazolidinedione coumarin hybrids as antidiabetic agent |
| topic | Molecular docking Molecular dynamics simulation DFT investigation α-glucosidase α-amylase DPP-4 |
| url | https://doi.org/10.1038/s41598-025-88944-y |
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